Understanding the gastrointestinal tract of the elderly to develop dietary solutions that prevent malnutrition

Although the prevalence of malnutrition in the old age is increasing worldwide a synthetic understanding of the impact of aging on the intake, digestion, and absorption of nutrients is still lacking. This review article aims at filling the gap in knowledge between the functional decline of the aging gastrointestinal tract (GIT) and the consequences of malnutrition on the health status of elderly. Changes in the aging GIT include the mechanical disintegration of food, gastrointestinal motor function, food transit, chemical food digestion, and functionality of the intestinal wall. These alterations progressively decrease the ability of the GIT to provide the aging organism with adequate levels of nutrients, what contributes to the development of malnutrition. Malnutrition, in turn, increases the risks for the development of a range of pathologies associated with most organ systems, in particular the nervous-, muscoskeletal-, cardiovascular-, immune-, and skin systems. In addition to psychological, economics, and societal factors, dietary solutions preventing malnutrition should thus propose dietary guidelines and food products that integrate knowledge on the functionality of the aging GIT and the nutritional status of the elderly. Achieving this goal will request the identification, validation, and correlative analysis of biomarkers of food intake, nutrient bioavailability, and malnutrition.info:eu-repo/semantics/publishedVersio

The effect of long-term ultra-endurance exercise and SOD2 genotype on telomere shortening with age

Telomere shortening, a well-known biomarker of aging, is a complex process influenced by several intrinsic and lifestyle factors. Although habitual exercise may promote telomere length maintenance, extreme endurance exercise has been also associated with increased oxidative stress—presumed to be the major cause of telomere shortening. Therefore, the pace of telomere shortening with age may also depend on antioxidant system efficiency, which is, in part, genetically determined. In this study, we aimed to evaluate the impact of ultra-endurance exercise and oxidative stress susceptibility (determined by the rs4880 polymorphism in the superoxide dismutase 2 (SOD2) gene) on telomere length. Genomic DNA was obtained from 53 sedentary individuals (34 females, 19–67 yr) and 96 ultra-trail runners (31 females, 23–58 yr). Indeed, blood samples before and after finishing a 107-km-trail race were collected from 69 runners to measure c-reactive protein (CRP) levels and, thus, analyze whether acute inflammation response is modulated by the SOD2 rs4880 polymorphism. Our results revealed that telomere length was better preserved in ultra-trail runners compared with controls, especially in elderly runners who have been regularly training for many years. Carrying the SOD2 rs4880*A allele was significantly associated with having shorter telomeres, as well as with having increased CRP levels after the ultra-trail race. In conclusion, habitual ultra-endurance exercise had a beneficial effect on telomere length maintenance, especially at older ages. This study also suggested that the SOD2 rs4880 polymorphism may also have an impact on acute and chronic oxidative-related damage (inflammatory response and telomere length) after an ultra-trail race. NEW & NOTEWORTHY Habitual ultra-endurance exercise seems to promote telomere length maintenance, especially at older ages. In addition, the beneficial effect of ultra-endurance training on biological aging is higher in ultra-trail runners who have been engaged to ultra-endurance training during many years. Finally, and for the first time, this study shows that the SOD2 rs4880 polymorphism has a significant impact on telomere length, as well as on acute inflammatory response to a 107-km trail race

Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial

Breast cancer; Metronomic; VinorelbineCáncer de mama; Quimioterapia metronómica; VinorelbinaCàncer de mama; Quimioteràpia metronòmica; VinorelbinaBackground: The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. Methods: Postmenopausal women with untreated stage I-III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures. Results: Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1-2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (- 73.2%) was superior to both monotherapy arms combined (- 49.9%; p = 0.001) and mVNB (- 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (- 73.2%) was numerically higher compared to LTZ (- 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases. Conclusions: Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted.This study was supported by a grant from Pierre-Fabre. Pierre-Fabre had no role in the management of this trial. The decisions and responsibilities of this trial were all under the sponsor: SOLTI Group

The effects of an invasive seaweed on native communities vary along a gradient of land-based human impacts

The difficulty in teasing apart the effects of biological invasions from those of other anthropogenic perturbations has hampered our understanding of the mechanisms underpinning the global biodiversity crisis. The recent elaboration of global-scale maps of cumulative human impacts provides a unique opportunity to assess how the impact of invaders varies among areas exposed to different anthropogenic activities. A recent meta-analysis has shown that the effects of invasive seaweeds on native biota tend to be more negative in relatively pristine than in human-impacted environments. Here, we tested this hypothesis through the experimental removal of the invasive green seaweed, Caulerpa cylindracea, from rocky reefs across the Mediterranean Sea. More specifically, we assessed which out of land-based and sea-based cumulative impact scores was a better predictor of the direction and magnitude of the effects of this seaweed on extant and recovering native assemblages. Approximately 15 months after the start of the experiment, the removal of C. cylindracea from extant assemblages enhanced the cover of canopy-forming macroalgae at relatively pristine sites. This did not, however, result in major changes in total cover or species richness of native assemblages. Preventing C. cylindracea re-invasion of cleared plots at pristine sites promoted the recovery of canopyforming and encrusting macroalgae and hampered that of algal turfs, ultimately resulting in increased species richness. These effects weakened progressively with increasing levels of land-based human impacts and, indeed, shifted in sign at the upper end of the gradient investigated. Thus, at sites exposed to intense disturbance from land-based human activities, the removal of C. cylindracea fostered the cover of algal turfs and decreased that of encrusting algae, with no net effect on species richness. Our results suggests that competition from C. cylindracea is an important determinant of benthic assemblage diversity in pristine environments, but less so in species-poor assemblages found at sites exposed to intense disturbance from landbased human activities, where either adverse physical factors or lack of propagules may constrain the number of potential native colonizers. Implementing measures to reduce the establishment and spread of C. cylindracea in areas little impacted by land-based human activities should be considered a priority for preserving the biodiversity of Mediterranean shallow rocky reefs

Alterações na adesão a Dieta Mediterrânica antes e depois do Confinamento por Covid 19

Apresentação em painelIntrodução - A Dieta Mediterrânica (DM) é considerada como um dos padrõesalimentares mais saudáveis e sustentáveis. A pandemia Covid-19 parece ter influenciado o comportamento alimentar em diversos países no sentido de um maior consumo de frutos e vegetais, assim como para uma maior disposição para cozinhar em casa. Objetivo -Pretendeu-se estudar o efeito do confinamento devido à pandemia Covid-19 na adesão à Dieta Mediterrânea e as alterações no consumo de alimentos característicos deste padrãoalimentar numa população portuguesa. Métodos - Os dados foram recolhidos online, pormeio de um inquérito de frequênciaalimentar antes do primeiro confinamento (PreC) eapós o último confinamento (PosC) devido à pandemia Covid-19. Foram elegíveis para análise participantes adultos, de nacionalidade portuguesa e residentes em Portugal (N PreC=500; N PosC=375). A adesão à DM foi calculada por meio do índice MEDAS (Mediterranean Diet Adhrence Screener). Resultados - Observou-se uma maior adesão à DM no período PosC, em relação ao período PreC (MEDAS PreC = 6,2±1,5 e MEDAS PosC=7,8 ±1.9; p<0,001). Dentro dos alimentos característicos da DM, observou-se um aumento significativo na frequência de consumo de vegetais (p=0,009), frutos frescos (p=0,011) e peixe (p=0,015). Foi também observada uma diminuição no consumo de bebidas açucaradas (p<0,001). Conclusão - Os resultados reforçam o efeito positivo da pandemia Covid-19 em hábitos alimentares saudáveis, com um aumento da adesão àDieta Mediterrânica.info:eu-repo/semantics/publishedVersio

Suppression of endogenous lipogenesis induces reversion of the malignant phenotype and normalized differentiation in breast cancer

Altres ajuts: We are greatly indebted to Prof. Robert A. Weinberg (Whitehead Institute for Biomedical Research, Cambridge, MA, USA) for providing the HMLERshCntrol and HMLERshEcad cells used in this work. Plan Nacional de I+D+I, Spain and the Departament d'Economia I Coneixement, Catalonia, Spain to Javier A. Menendez. Elisabet Cuyàs is the recipient of a "Sara Borrell" post-doctoral contract (CD15/00033, Ministerio de Sanidad y Consumo, Fondo de Investigación Sanitaria -FIS-, Spain).The correction of specific signaling defects can reverse the oncogenic phenotype of tumor cells by acting in a dominant manner over the cancer genome. Unfortunately, there have been very few successful attempts at identifying the primary cues that could redirect malignant tissues to a normal phenotype. Here we show that suppression of the lipogenic enzyme fatty acid synthase (FASN) leads to stable reversion of the malignant phenotype and normalizes differentiation in a model of breast cancer (BC) progression. FASN knockdown dramatically reduced tumorigenicity of BC cells and restored tissue architecture, which was reminiscent of normal ductal-like structures in the mammary gland. Loss of FASN signaling was sufficient to direct tumors to a reversed phenotype that was near normal when considering the development of polarized growth-arrested acinar-like structure similar to those formed by nonmalignant breast cells in a 3D reconstituted basement membrane in vitro. This process, in vivo, resulted in a low proliferation index, mesenchymal-epithelial transition, and shut-off of the angiogenic switch in FASN-depleted BC cells orthotopically implanted into mammary fat pads. The role of FASN as a negative regulator of correct breast tissue architecture and terminal epithelial cell differentiation was dominant over the malignant phenotype of tumor cells possessing multiple cancer-driving genetic lesions as it remained stable during the course of serial in vivo passage of orthotopic tumor-derived cells. Transient knockdown of FASN suppressed hallmark structural and cytosolic/secretive proteins (vimentin, N-cadherin, fibronectin) in a model of EMT-induced cancer stem cells (CSC). Indirect pharmacological inhibition of FASN promoted a phenotypic switch from basal- to luminal-like tumorsphere architectures with reduced intrasphere heterogeneity. The fact that sole correction of exacerbated lipogenesis can stably reprogram cancer cells back to normal-like tissue architectures might open a new avenue to chronically restrain BC progression by using FASN-based differentiation therapies

Modeling the observed tropospheric BrO background: Importance of multiphase chemistry and implications for ozone, OH, and mercury

Aircraft and satellite observations indicate the presence of ppt (ppt ≡ pmol/mol) levels of BrO in the free troposphere with important implications for the tropospheric budgets of ozone, OH, and mercury. We can reproduce these observations with the GEOS-Chem global tropospheric chemistry model by including a broader consideration of multiphase halogen (Br–Cl) chemistry than has been done in the past. Important reactions for regenerating BrO from its non-radical reservoirs include HOBr+Br−/Cl− in both aerosols and clouds, and oxidation of Br− by ClNO3 and ozone. Most tropospheric BrO in the model is in the free troposphere, consistent with observations, and originates mainly from the photolysis and oxidation of ocean-emitted CHBr3. Stratospheric input is also important in the upper troposphere. Including production of gas phase inorganic bromine from debromination of acidified sea salt aerosol increases free tropospheric Bry by about 30 %. We find HOBr to be the dominant gas-phase reservoir of inorganic bromine. Halogen (Br-Cl) radical chemistry as implemented here in GEOS-Chem drives 14 % and 11 % decreases in the global burdens of tropospheric ozone and OH, respectively, a 16 % increase in the atmospheric lifetime of methane, and an atmospheric lifetime of 6 months for elemental mercury. The dominant mechanism for the Br-Cl driven tropospheric ozone decrease is oxidation of NOx by formation and hydrolysis of BrNO3 and ClNO3

Significant Clinical Activity of Olaparib in a Somatic BRCA1-Mutated Triple-Negative Breast Cancer With Brain Metastasis

Breast cancer is a biologically and clinically heterogeneous disease, and patients with similar clinical stage have markedly different outcomes. Triple-negative breast cancer (TNBC) is defined by the lack of expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2).1,2 This subtype represents 15% to 20% of all breast cancers and is associated with the worst outcome of all subtypes, with greater tendency to distant recurrence in general and visceral metastasis in particular, including brain metastasis.3,4 To date, chemotherapy remains the standard of care for TNB